With the progress of social modernization and the pace acceleration of people's daily life, an increasing number of accidents, resulting from traffic, industry, and sports, local wars, violent events, and natural disasters (e.g. earthquakes), will lead to peripheral nerve injury. When the formed nerve defect of middle and long distance cannot be treated by end-to-end suture in the clinic, peripheral nerve grafting has to be applied to bridge the nerve defect. Although nerve grafts have been searched for and developed for more than a hundred years, great efforts are still devoted to the development of ideal nerve grafts to substitute autologous nerve grafts in clinical practice. Despite being a golden standard for peripheral nerve repair, autologous nerve grafting can not be widely used in the clinic due to its several limitations, such as deficient supply of donor nerves, mismatch between the injured nerve and the donor nerve in the structure and size, as well as donor site morbidity and secondary deformities.
The emergence and advance of the tissue engineering field provide a unique opportunity to generate a tissue engineered nerve grafts as a promising alternative to autologous nerve grafts. The existing tissue engineered grafts mainly include two important types. One type is the acellular allogeneic nerve, i.e. acellular nerve graft (ANG), in which the cells in the allogeneic tissue are removed but the original neural architecture was kept. The ANG meets the basic requirements for nerve grafts in peripheral nerve tissue engineering, and becomes aft tissue-derived ECM modified tissue engineered nerve grafts. For example, a research article has indicated that ANG induces differentiation of adult rat BMSCs into Schwann cells (He Hongyun, Deng Yihao, Ke Xiaojie, et al, Morphologic Study of Bone Marrow Stromal Cells of Rat Differentiating into Schwann Cells By Acellularnerve Grafts. Chinese Journal of Neuroanatomy, 2007; 23(6):). Another study investigates the protective effects of the implanted ANG on motor neurons of the anterior horn of the spinal cord (Liu Jinchao, Lin Xiaoping, Ke Xiaojie, et al. The Protective Effects of Acellularnerve Matrix Allografts on the Motor Neurons of the Anterior Horn of Spinal Cord Progress of Anatomical Sciences, 2005(3): 206-209), and indicates that the use of ANGs to bridge peripheral nerve defects has had excellent protective effects on the survival of the cell body of motor neurons. Although there are a large number of studies on the preparation technology of ANGs achieving the faster progress, many preparation methods have complicated procedures, and the fine structure and mechanical properties of biomaterials will be impacted during processing.
Another type is based on a nerve conduit prepared with a proper mould and having ECM or support cells coated on its inner and outer surfaces. For example, a research article reports on the use of a bridge graft made up of olfactory ensheathing cells (OECs)-Schwann cells (SCs) derived ECM and poly(DLlactide-co-glycolide acid) (PLGA) to protect the peripheral target organs and spinal cord neurons after sciatic nerve injury (You Hua, Jiao Shusheng, Feng Shuainan, et al, The Protective Effects of Tissue Engineering Artificial Nerves on Peripheral Target Organs and Spinal Cord Neurons after Sciatic Nerve Defect Chinese Journal of Trauma, 2010 Vol. 26 No. 3 P. 265-269) As another example, a Chinese patent (an application No. of CN03134541.7 and an application publication No of CN1589913) entitled “A tissue engineering peripheral nerve used for repairing peripheral nerve defect and its preparation method” describes a tissue engineered nerve used for repairing peripheral nerve defect. The tissue engineered nerve consists of a nerve conduit made of biodegradable materials added with glial cells or stem cells having ability to differentiate into glial cells, which are used as seed cells, and modified with microspheres for controlled release of neurotrophic factors and with ECM molecules.
At present, support cells used in the tissue engineered nerves include Schwann cells and various stem cells, which are allogeneic cells, and may cause immunogenicity, which is not suitable for clinic applications. On the other hand, the in vivo fate and biological effects of support cells after they are implanted into the body are not fully clear, and they may be inactivated in the environment of the body, thus failing to achieve expected biological effects. All the above issues limit the development of tissue engineered nerve grafts.